2.1. Gorlin-Chaudhry-Moss syndrome

At least two mutations in the SLC25A24 gene have been found to cause Gorlin-Chaudhry-Moss syndrome. This condition, which has been found only in females, is characterized by skull abnormalities that affect the shape of the head and face, a lack of fatty tissue under the skin (lipodystrophy), excessive hair growth (hypertrichosis) on the face and body, shortened bones at the ends of the fingers and toes (short distal phalanges), and smaller-than-normal external female genital folds (hypoplasia of the labia majora).

The mutations that cause Gorlin-Chaudhry-Moss syndrome change a single protein building block (amino acid) in the ATP-Mg/Pi carrier protein. The mutations change the amino acid arginine at position 217 to either the amino acid histidine (written as Arg217His or R217H) or the amino acid cysteine (written as Arg217Cys or R217C). These mutations are thought to alter the structure of the protein, which likely decreases its ability to transport molecules across the mitochondrial inner membrane. As a result, there is an increase in mitochondrial size (mitochondria swelling), breakage of mitochondria into smaller pieces, and an overall decrease in ATP production. This increase in abnormal mitochondria and decrease in energy production can lead to cell death.

While altered cellular energy production and increased cell death are likely responsible for the features of Gorlin-Chaudhry-Moss syndrome, it is unclear how these changes lead to the specific signs and symptoms of the condition.

2.2. Other disorders

The same two SLC25A24 gene mutations that cause Gorlin-Chaudhry-Moss syndrome (described above) have been found in individuals with a similar disorder known as Fontaine syndrome or Petty-type congenital progeroid syndrome. This syndrome has many of the same features of Gorlin-Chaudhry-Moss syndrome, including skull abnormalities, lipoatrophy, and short distal phalanges, but includes normal genital development and sparse hair, and affects boys and girls equally. Also, in contrast to Gorlin-Chaudhry-Moss syndrome, individuals with Fontaine syndrome typically do not survive past infancy.

It is unclear how the same mutations can lead to different disorders. Researchers suspect that variations in other genes involved in mitochondrial function may play a role as well as other genetic and environmental factors.